Serum cholesterol binding reserve (SCBR), the amount of additional cholesterol which a serum sample can solubilize, was measured in middle-aged male diabetic patients. The values were compared with those of non-diabetic controls. When the data were stratified according to serum levels of cholesterol and triglycerides, lower SCBR values were observed in patients at each lipid level, and a statistically significant difference (p less than 0.05) was observed between patients (mean plus or minus SD, 87 plus or minus 40) and controls (mean plus or minus SD, 57 plus or minus 16) having serum cholesterol between 200 and 250 mg/dl and triglycerides below 150 mg/dl. When each patient was paired with a control subject with matching serum levels of cholesterol and triglycerides to within 5 mg/dl, lower SCBR was found in the patient in 17 of 22 pairs (p less than 0.01). These results indicate an association of decreased SCBR with diabetes mellitus independent of the association of hyperlipidemia with the disease, and suggest that low SCBR may be a risk factor for coronary heart disease in these patients. Collection of additional data is in progress.